The vast majority of experimental data concerning periodontal diseases is based on studies of humans or bacteria isolated from humans. Relatively little is known with respect to periodontal disease in non-human animals, such as companion animals, and in particular, dogs and cats.
Periodontal disease comprises a group of infections involving supporting tissues of the teeth. These range in severity from mild and reversible inflammation of the gingiva (gum) to chronic destruction of periodontal tissues (gingiva, periodontal ligament, and alveolar bone) with eventual exfoliation of teeth.
From a microbiological standpoint, several features of this disease are of interest. The bacterial etiology is complex, with a variety of organisms responsible for the initiation and progression of disease in humans. Many, if not all, of these organisms may also be present in periodontally healthy individuals and can exist in commensal harmony with the host. Thus, disease episodes may ensue from a shift in the ecological balance between bacterial and host factors, as a result of, for example, alteration in the absolute or relative numbers of certain organisms, changes in pathogenic potential, or modulation of particular host factors. The local environment imposes a variety of unique constraints upon the constituent microbiota of the supragingival tooth surface and the subgingival crevice (the channel between the tooth root and the gingiva that deepens into a periodontal pocket as disease progresses).
Both the calcified hard tissues of the tooth and the epithelial cells of the gingival are available for colonization. These tissues are exposed to host salivary secretions and gingival crevicular fluid (a serum exudate), both of which contain molecules that interact directly with bacteria and alter prevailing environmental conditions. In addition, it is known that in humans, successful colonizers of the teeth and subgingival area must coexist with many (over 600) other species of bacteria that inhabit these regions. Study of the pathogenesis of periodontal diseases in humans is thus complicated by the ecological intricacy of the microenvironment.
The classification of the various manifestations of periodontal disease in humans is continually changing, and it will suffice to mention that diseases range in severity, rate of progression, and number of teeth affected and that different age groups can be susceptible following the eruption of primary teeth. The nature of the pathogenic agents varies among these disease entities, as well as among human patients and even between different disease sites within a patient. In general, however, severe forms of the disease are associated with a number of gram-negative anaerobic bacteria. Of this group, in humans, most evidence points to a pathogenic role for Porphyromonas (formerly Bacteroides) gingivalis. The presence of this organism, acting either alone or as a mixed infection with other bacteria, and possibly in concert with the absence of beneficial species and certain immunological responses in the host, appears to be essential for disease activity.
Colonization of the oral cavity requires that the bacteria first enter the mouth and then localize at and attach to the available surfaces. Host factors which function to prevent bacterial colonization include the mechanical shearing forces of tongue movement along with saliva and gingival crevicular fluid flow. Successful oral colonizers therefore possess a variety of attributes to overcome host protective mechanisms. The sessile plaque biofilm that subsequently accumulates on the hard and soft tissues of the mouth is a dynamic system composed of diverse microbial species. In humans, P. gingivalis is usually among the late or secondary colonizers of the oral cavity, requiring antecedent organisms to create the necessary environmental conditions.
Initial entry of P. gingivalis into the human oral cavity is thought to occur by transmission from infected individuals. Other vectors would therefore also appear to be operational. These studies indicate that individuals are colonized by a single (or at least a predominant) genotype, regardless of site of colonization or clinical status. Strains of many different clonal origins, in contrast, are present in different individuals. This supports the concept that P. gingivalis is essentially an opportunistic pathogen, with virulence not being restricted to a particular clonal type.
The human oral cavity provides a variety of surfaces to which P. gingivalis can adhere. There are the mineralized hard tissues of the teeth, along with mucosal surfaces including those of the gingiva, cheek, and tongue.
While a great deal is known about periodontal disease in humans, as described above, very little is known about the same disease in companion animals. Fournier, D. et al., “Porphorymonas gulae sp. nov., an Anaerobic, Gram-negative, Coccibacillus from the Gingival Sulcus of Various Animal Hosts”, International Journal of a Systematic and Evolutionary Microbiology (2001), 51, 1179-1189 describe several strains isolated from various animal hosts, including a strain, P. gulae spp. nov., designated ATCC 57100. The authors hypothesize that strains for the animal biotype of P. gingivalis represent a Porphyromonas species that is distinct from P. gingivalis. There is no mention of a vaccine useful in treating periodontal disease in companion animals. Hirasawa and Takada, in “Porphyromonas gingivicanis sp. nov. and Porphyromonas crevioricanis sp. nov., Isolated from Beagles”, International Journal of Systemic Bacteriology, pp. 637-640, (1994), describe two bacterial species isolated from gingival crevicular fluids of beagles. These species are described in U.S. Pat. Nos. 5,710,039 and 5,563,063. Nowhere do the authors suggest the use of these species in a vaccine to treat periodontal disease. International Application PCT/AU98/01023, having publication number WO 99/29870, described various P. gingivalis polypeptides and nucleotides. However, no evidence of vaccines effective in preventing periodontal disease in companion animals is provided. Even though there is a great amount of information known about the human disease, little has been accomplished by way of preventing or treating the disease, even in humans.
There remains a need for a safe and effective vaccine for treating and preventing periodontal disease in companion animals.
Genco et al. (Trends in Microbiology 6: 444-449, 1998) describe a rat model for investigating Porphyromonas gingivicanis-mediated periodontal disease. Grecca et al. (J. Endodontics 27: 610, 2001) describe radiographic evaluation of periradicular repair after endodontic treatment of dog's teeth with induced periradicular periodontitis.
Prior to the present invention, there has been no animal model available for assessing the efficacy of a vaccine against one or more periopathogenic bacteria in a defined and quantitative manner.